HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 47, 34048-34057, November 23, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/47/34048    most recent M702384200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Prulière-Escabasse, V. Articles by Clerici, C. Search for Related Content PubMed PubMed Citation Articles by Prulière-Escabasse, V. Articles by Clerici, C. Social Bookmarking                      What's this?

Modulation of Epithelial Sodium Channel Trafficking and Function by Sodium 4-Phenylbutyrate in Human Nasal Epithelial Cells^*

Virginie Prulière-Escabasse^¶1, Carole Planès^||**, Estelle Escudier, Pascale Fanen, André Coste^¶, and Christine Clerici^¶¶

From the INSERM, U 841, Créteil, F-94000, the Université Paris 12, Créteil F-94000, the ^¶Service d'Oto-Rhino-Laryngologie et de Chirurgie Cervico-Faciale, Hôpitaux Henri Mondor (Assistance Publique-Hôpitaux de Paris) et Intercommunal, Créteil F-94000, the ^||Université Versailles, Saint Quentin, F-78000, ^**Assistance Publique-Hôpitaux de Paris, Hôpital Ambroise Paré, Service de Physiologie, Boulogne F-92220, INSERM, U 773, CRB3, Paris, F-75018, the Université Denis Diderot-Paris 7, F-75013, and ^¶¶Assistance Publique-Hôpitaux de Paris, Hôpital Bichat-Claude Bernard, Service de Physiologie, Paris, F-75018, France

Sodium 4-phenylbutyrate (4-PBA) has been shown to correct the cellular trafficking of several mutant or nonmutant plasma membrane proteins such as cystic fibrosis transmembrane conductance regulator through the expression of 70-kDa heat shock proteins. The objective of the study was to determine whether 4-PBA may influence the functional expression of epithelial sodium channels (ENaC) in human nasal epithelial cells (HNEC). Using primary cultures of HNEC, we demonstrate that 4-PBA (5 mM for 6 h) markedly stimulated amiloride-sensitive sodium channel activity and that this was related to an increased abundance of -, -, and -ENaC subunits in the apical membrane. The increase in ENaC cell surface expression (i) was due to insertion of newly ENaC subunits as determined by brefeldin A experiments and (ii) was not associated with cell surface retention of ENaC subunits because endocytosis of ENaC subunits was unchanged. In addition, we find that ENaC co-immunoprecipitated with the heat shock protein constituvely expressed Hsc70, that has been reported to modulate ENaC trafficking, and that 4-PBA decreased Hsc70 protein level. Finally, we report that in cystic fibrosis HNEC obtained from two cystic fibrosis patients, 4-PBA increased functional expression of ENaC as demonstrated by the increase in amiloride-sensitive sodium transport and in -, -, and -ENaC subunit expression in the apical membrane. Our results suggest that in HNEC, 4-PBA increases the functional expression of ENaC through the insertion of new -, -, and -ENaC subunits into the apical membrane and also suggest that 4-PBA could modify ENaC trafficking by reducing Hsc70 protein expression.

Received for publication, March 20, 2007 , and in revised form, September 17, 2007.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Service d'Oto-Rhino-Laryngologie et de Chirurgie Cervico-Faciale, Hôpitaux Henri Mondor (AP-HP) et Intercommunal, 51 avenue du Maréchal de Lattre de Tassigny, 94010 Créteil Cedex, France. Tel.: 33-1-49-81-36-37; Fax: 33-1-48-98-17-77; E-mail: virginie.pruliere{at}creteil.inserm.fr.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				V. Bhalla and K. R. Hallows Mechanisms of ENaC Regulation and Clinical Implications J. Am. Soc. Nephrol., October 1, 2008; 19(10): 1845 - 1854. [Abstract] [Full Text] [PDF]

				T. Roque, E. Boncoeur, V. Saint-Criq, E. Bonvin, A. Clement, O. Tabary, and J. Jacquot Proinflammatory Effect of Sodium 4-Phenylbutyrate in {Delta}F508-Cystic Fibrosis Transmembrane Conductance Regulator Lung Epithelial Cells: Involvement of Extracellular Signal-Regulated Protein Kinase 1/2 and c-Jun-NH2-Terminal Kinase Signaling J. Pharmacol. Exp. Ther., September 1, 2008; 326(3): 949 - 956. [Abstract] [Full Text] [PDF]